Pontocerebellar Hypoplasia Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
5051 AMPD2 81479,81479 Order Options and Pricing
CHMP1A 81479,81479
CLP1 81479,81479
EXOSC3 81479,81479
RARS2 81479,81479
SEPSECS 81479,81479
TSEN15 81479,81479
TSEN2 81479,81479
TSEN34 81479,81479
TSEN54 81479,81479
VPS53 81479,81479
VRK1 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
5051Genes x (12)81479 81479 $890 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Pontocerebellar hypoplasias (PCH) are a group of clinically and genetically heterogeneous neurodegenerative disorders characterized by abnormal development of the pons, cerebellum and cerebral cortex; progressive microcephaly; psychomotor developmental delay; and swallowing difficulties (Barth. 1993. PubMed ID: 8147499; Namavar et al. 2011. PubMed ID: 21368912). Several subtypes have been described based on the clinical presentation, progression, and pathological and molecular defects. However, clinical overlapping features among various subtypes have been reported, and some genes have been implicated in more than one subtype, suggesting that PCH constitute a spectrum (Burglen et al. 2012. PubMed ID: 22452838; Samanta and Willis. 2016. PubMed ID: 27570394). Distinguishing features for the various subtypes are listed in the individual gene Test Descriptions.

Genetics

All pontocerebellar hypoplasias are transmitted with an autosomal recessive mode of inheritance. Defects in the following genes have been documented as causative for the disorder: AMPD2, CHMP1A, CLP1, EXOSC3, RARS2, SEPSECS, TSEN2, TSEN15, TSEN34, TSEN54, VPS53, and VRK1. To date, about 80 causative variants have been reported. About half the variants are missense; the other half comprise variants that are predicted to result in truncated proteins and include substitutions leading to premature stop codons, small deletions/insertions, splicing variants and two large deletions (Human Gene Mutation Database). Information on molecular biology of gene products is provided in individual gene test descriptions.

Clinical Sensitivity - Sequencing with CNV PGxome

Pathogenic variants in the EXOSC3 gene were detected in 60% of patients with a clinical diagnosis of PCH1 (Wan et al. 2012. PubMed ID: 22544365).

Pathogenic variants in the AMPD2 gene have been reported in 16% of patients with a clinical diagnosis of Pontocerebellar Hypoplasia (PCH) (Akizu et al. 2013. PubMed ID: 23911318).

Pathogenic variants in the TSEN54 gene account for over 90% of patients with PCH2 and PCH4 (Budde et al. 2008. PubMed ID: 18711368; Namavar et al. 2016. PubMed ID: 20301773). PCH5 appears to be rare. Only one family with PCH5 and pathogenic variants in TSEN54 has been reported to date (Namavar et al. 2011. PubMed ID: 21368912).

Pathogenic variants in the TSEN34 gene account for less than 2% of patients with PCH2 (Namavar et al. 2011. PubMed ID: 20952379). To date, only one homozygous missense variant was reported in a patient of Turkish origin (Budde et al. 2008. PubMed ID: 18711368).

Pathogenic variants in the TSEN2 gene account for less than 2% of patients with PCH2 (Namavar et al. 2011. PubMed ID: 20952379).

A total of 29 patients with pathogenic variants in the RARS2 gene have been described worldwide (van Dijk et al. 2017. PubMed ID: 27683254).

Pathogenic variants in the SEPSECS gene have been reported in a total of 13 unrelated patients with PCH (Iwama et al. 2016. PubMed ID: 26888482; Human Gene Mutation Database).

Three missense variants in the TSEN15 gene were found in three unrelated consanguineous families with a history of the PCH (Breuss et al. 2016. PubMed ID: 27392077).

Two pathogenic variants in the VPS53 gene have been implicated in PCH. They appear to be common in the Jewish Moroccan population with a carrier rate of ~ 1:37 (Feinstein et al. 2014. PubMed ID: 24577744).

Only two truncating variants in the CHMP1A gene have been reported to be causative of PCH in 3 families from Peru and Puerto Rico (Mochida et al. 2012. PubMed ID: 23023333).

Two variants in the VRK1 gene have been implicated in PCH. They appear to be rare (Renbaum et al. 2009. PubMed ID: 19646678; Najmabadi et al. 2011. PubMed ID: 21937992).

One pathogenic missense variant in the CPL1 gene has been reported to be the cause of PCH10 in nine, apparently unrelated, consanguineous families from the Middle East (Schaffer et al. 2014. PubMed ID: 24766810; Karaca et al. 2014. PubMed ID: 24766809).

Pathogenic copy number variants have been reported only in the EXOSC3 and SEPSECS genes (Eggens. 2014. PubMed ID: 24524299; Iwama et al. 2016. PubMed ID: 26888482).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel typically provides 98.0% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Candidates for this test are patients with pontocerebellar hypoplasia and a family history consistent with autosomal recessive mode of inheritance.

Genes

Official Gene Symbol OMIM ID
AMPD2 102771
CHMP1A 164010
CLP1 608757
EXOSC3 606489
RARS2 611524
SEPSECS 613009
TSEN15 608756
TSEN2 608753
TSEN34 608754
TSEN54 608755
VPS53 615850
VRK1 602168
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • Akizu et al. 2013. PubMed ID: 23911318
  • Barth. 1993. PubMed ID: 8147499
  • Breuss et al. 2016. PubMed ID: 27392077
  • Budde et al. 2008. PubMed ID: 18711368
  • Burglen et al. 2012. PubMed ID: 22452838
  • Eggens et al. 2014. PubMed ID: 24524299
  • Feinstein et al. 2014. PubMed ID: 24577744
  • Human Gene Mutation Database (Bio-base).
  • Iwama et al. 2016. PubMed ID: 26888482
  • Karaca et al. 2014. PubMed ID: 24766809
  • Mochida et al. 2012. PubMed ID: 23023333
  • Najmabadi et al. 2011. PubMed ID: 21937992
  • Namavar et al. 2011. PubMed ID: 21368912
  • Namavar et al. 2016. PubMed ID: 20301773
  • Namavar Y. et al. 2011. PubMed ID: 20952379
  • Renbaum et al. 2009. PubMed ID: 19646678
  • Samanta and Willis. 2016. PubMed ID: 27570394
  • Schaffer et al. 2014. PubMed ID: 24766810
  • van Dijk et al. 2017. PubMed ID: 27683254

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

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